1vyq

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[[Image:1vyq.gif|left|200px]]<br /><applet load="1vyq" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1vyq.gif|left|200px]]
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caption="1vyq, resolution 2.4&Aring;" />
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'''NOVEL INHIBITORS OF PLASMODIUM FALCIPARUM DUTPASE PROVIDE A PLATFORM FOR ANTI-MALARIAL DRUG DESIGN'''<br />
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{{Structure
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|PDB= 1vyq |SIZE=350|CAPTION= <scene name='initialview01'>1vyq</scene>, resolution 2.4&Aring;
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|SITE= <scene name='pdbsite=AC1:Dux+Binding+Site+For+Chain+A'>AC1</scene>
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|LIGAND= <scene name='pdbligand=DUX:2,3-DEOXY-3-FLUORO-5-O-TRITYLURIDINE'>DUX</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23]
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|GENE=
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}}
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'''NOVEL INHIBITORS OF PLASMODIUM FALCIPARUM DUTPASE PROVIDE A PLATFORM FOR ANTI-MALARIAL DRUG DESIGN'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1VYQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=DUX:'>DUX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] Known structural/functional Site: <scene name='pdbsite=AC1:Dux+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VYQ OCA].
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1VYQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VYQ OCA].
==Reference==
==Reference==
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dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors., Whittingham JL, Leal I, Nguyen C, Kasinathan G, Bell E, Jones AF, Berry C, Benito A, Turkenburg JP, Dodson EJ, Ruiz Perez LM, Wilkinson AJ, Johansson NG, Brun R, Gilbert IH, Gonzalez Pacanowska D, Wilson KS, Structure. 2005 Feb;13(2):329-38. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15698576 15698576]
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dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors., Whittingham JL, Leal I, Nguyen C, Kasinathan G, Bell E, Jones AF, Berry C, Benito A, Turkenburg JP, Dodson EJ, Ruiz Perez LM, Wilkinson AJ, Johansson NG, Brun R, Gilbert IH, Gonzalez Pacanowska D, Wilson KS, Structure. 2005 Feb;13(2):329-38. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15698576 15698576]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: plasmodium falciparum]]
[[Category: plasmodium falciparum]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:43 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:49:52 2008''

Revision as of 12:49, 20 March 2008

Image:1vyq.gif


PDB ID 1vyq

Drag the structure with the mouse to rotate
, resolution 2.4Å
Sites:
Ligands:
Activity: dUTP diphosphatase, with EC number 3.6.1.23
Coordinates: save as pdb, mmCIF, xml



NOVEL INHIBITORS OF PLASMODIUM FALCIPARUM DUTPASE PROVIDE A PLATFORM FOR ANTI-MALARIAL DRUG DESIGN


Overview

Pyrimidine metabolism is a major route for therapeutic intervention against malaria. Here we report inhibition and structural studies on the deoxyuridine nucleotidohydrolase from the malaria parasite Plasmodium falciparum (PfdUTPase). We have identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which inhibit specifically the Plasmodium dUTPase versus the human enzyme. A 2.4 Angstrom crystal structure of PfdUTPase in complex with one of these inhibitors reveals an atypical trimeric enzyme in which the triphenylmethane derivative can be seen to select for PfdUTPase by way of interactions between the trityl group and the side chains of residues Phe46 and Ile117. Immunofluorescence microscopy studies of parasitized red blood cells reveal that enzyme concentrations are highest during the trophozoite/schizont stages, suggesting that PfdUTPase has a major role in DNA replication. Taken together the data show that PfdUTPase may be considered as an antimalarial drug target.

About this Structure

1VYQ is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

Reference

dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors., Whittingham JL, Leal I, Nguyen C, Kasinathan G, Bell E, Jones AF, Berry C, Benito A, Turkenburg JP, Dodson EJ, Ruiz Perez LM, Wilkinson AJ, Johansson NG, Brun R, Gilbert IH, Gonzalez Pacanowska D, Wilson KS, Structure. 2005 Feb;13(2):329-38. PMID:15698576

Page seeded by OCA on Thu Mar 20 14:49:52 2008

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